Chinese and Western medicine treatment of blocking antibody in recurrent spontaneous abortion

Ping Shng(平尚), nd Feng Xioling(冯晓玲)

Chinese and Western medicine treatment of blocking antibody in recurrent spontaneous abortion

Ping Shang(平尚)a, and Feng Xiaoling(冯晓玲)b

a: Heilongjiang university of Chinese medicine, Harbin 150040, China

b: The first hospital affiliated to Heilongjiang university of Chinese medicine, Harbin 150040, China

The causes of recurrent spontaneous abortion are complex traditional Chinese medicine holds that its etiology is losses of spleen and kidney qi, qi and xue deficiency, in addition to secretion, genetic, anatomical, infection, systemic diseases, environmental factors and other related immune factors, the def i ciency of blocking antibody is also one of the reasons for the lack of immune factors. In treating it, Chinese medicine treatment combines the patients personal constitution and treatment based on syndrome dif f erentiation; Western medicine treatment mainly applies Aspirin, active immune lymphocyte treatment, low molecular heparin, gamma globulin protein passive immune treatment and psychological intervention therapy. In this paper, a review of the treatment methods for closed antibodies in the past 5 years is made.

Recurrent spontaneous abortion; Blocking antibody; Treatment based on syndrome differentitation; Lymphocyte Immunotherapy; Intravenous Immunoglobulin

Recurrent spontaneous abortion (RSA) refers to spontaneous abortion that occurs 3 times continuously or more than 3 times. The majority of RSA patients suf f er from early miscarriage while minority of patients suf f er from late-term abortion.1 It is one of the common complications of pregnancy. The causes of RSA include chromosomal abnormalities, corpus luteum the function is not complete, low thyroid function, anatomy, infection and immune factors and so on, which indicate that immune contains same immune and autoimmune. The same immune is the major cause of the deficiency of Blocking Antibody (BA). There are many disputes in the treatment of blocking antibody. This paper summarizes the experience of Chinese and western medicine in the treatment of blocking antibody, which combined the individual clinical experience and the clinical experiment.

THE TRADITIONAL CHINESE MEDICINE TREATMENT

Treatment of personal experience

Zhang Jinfeng2summarized the shafts and Chinese medicine's clinical experience in the treatment of insufficient blocking antibody recurrent miscarriage, treatment can be divided into three principles, the fi rst method: nourishing blood and activating blood, removing stasis and giving birth to the new blood; The second method, tonifying qi and blood, tonifying kidney and solidifying root; The third method: tonifying qi and blood, tonifying kidney and solidifying embryo. Sun Lixin3held that the kidney def i ciency was the root of insufficient blocking antibody, which caused kidney deficiency that could not solidify the embryo, which fi nally led to a difficult condition. For such cases, the treatment can be divided into two parts, the fi rst part: which caused kidney def i ciency that could not solidify the embryo,which finally led to a difficult condition, which prepared for the pregnancy and guided the pregnancy with patients; the second part: in pregnant drought tocolysis treatment, modified Taishan rock powder based on the changes of patient-specif i c symptoms was applied, which achieved satisfactory clinical results. Zhang Guanyin4, in the treatment of kidney def i ciency and blood stasis in patients with recurrent abortion, Chose decoction to tonify kidney, activate blood and solidify embryo, and the formula varied based on the change of clinical symptoms of patients in the treatment of 0 cases of patients with recurrent abortion, which achieved a total ef f ective rate of 94% based on syndrome differentiation treatment, and combined with Xi Guicheng5“Chinese medicine cycle therapy”, there was considerable improvement in the positive rate and pregnancy success rate of patients with blocking antibody. Ping Jiang6summarized Ping Fu’s experience of treating low blocking antibody in recurrent abortion and pointed out that the kidney Yang def i ciency was the root of the disease, therefore, appropriate choice to tonify qi and solidify kidney and warm yang was the principle in treatment, and this method obtained very good clinical effect. Professor Yingchen7treated the lack of BA patients by applying decoction to tonify kidney and strengthen spleen and remove stasis, whichachieved very good clinical curative ef f ect. Professor He Jialin8paid attention to conditioning before pregnancy in the treatment of patients with insufficient blocking antibody by giving priority to tonifying kidney and strengthening spleen, nourishing blood and harmonizing chong, and after pregnancy, priority was given to tonifying kidney and strengthening spleen and solidifying chong, tonifying qi and nourishing blood, this method had achieved good clinical efficacy. Ping Fu9used Yulin Decoction to treat insufficient blocking antibody in patients with recurrent abortion before pregnancy by improving the level of blocking antibody and the pregnancy outcome.

Treatment based on syndrome dif f erentiation

Treatment based on syndrome dif f erentiation is the important principle and method of traditional Chinese medicine diagnosis and treatment of disease, it is also traditional Chinese medicine academic characteristic and essence, so it is possible to treat different diseases with the same formula, and to treat a disease with dif f erent formulas, which has obtained good clinical curative effect. Scholars summarized their syndrome differentiation methods according to their understanding of the disease etiology, pathogenesis and clinical experience. Lu Qibin10treated recurrent abortion patients of spleen and kidney deficiency and blood hot clip stasis with Anzi mixture, which significantly relieved the clinical symptoms, promoted blocking antibody to turn positive; Cao Peixia11applied tonifying kidney and activating blood therapy on patients with loss of blood stasis type BA and increased the BA turning positive rate; Liu Chunxiang12used warming kidney and tonifying Yang principle in the treatment of insufficient blocking antibody, clinical analysis after treatment indicated that it could improve the success rate of pregnancy of patients and enhance blocking antibody positive rate, reduce the rate of abortion. Shao Shuqin13used tonifying kidney and clearing heat method in the treatment of 30 cases of blocking antibody insufficient patients with recurrent abortion, after which the pregnancy success rate was 86.7%, and the blocking antibody turning positive rate was 93.33%. Lv Chunying14adapted tonifying kidney and strengthening spleen method in treating BA negative patients, the clinical manifestation of patients improved clinically, and spleen and kidney deficiency disappeared and it took a shorter time for BA turning positive. Qian Luli15used Angong Formula in treating 22 cases of spleen and kidney def i ciency and blood stasis patients, after which the blocking antibody positive rate was 83.36%. Lv Beili16used tonifying kidney and activating blood formula in the treatment of recurrent abortion patients with negative blocking antibody, after a month of treatment, blocking antibody BE- Ab1 and BE - Ab2 were statistically signif i cant, 35 cases in the treatment group were cured. Gao Hanyi17used Tiaomian Sanhao in treating recurrent abortion patients with kidney and spleen def i ciency type blocking antibodies, after 3 months’ treatment, the blocking antibody positive rate was 87.1%, 1 year successful pregnancy rate was 58.1%, which was better than treatment with active immune ef f ect.

Modif i ed formula

Many scholars use modif i ed formula to treat blocking antibody negative patients with recurrent abortion. Bao Fenhong18used tonifying kidney and strengthening spleen method in the treatment of insufficient BA with RSA in the clinical research, the formula was combined with Shoutai Pill and Taishan Rock Powder, which achieved significant effect on the improvement of the clinical syndrome and increased pregnancy success rate. Zhang Hong19added and subtracted the formula by using Shoutai Pill in the treatment of patients with a history of miscarriage and low BA threatened abortion, which achieved good clinical efficacy. Zhang Aiping20used the Taohong Siwu decoction in treating 32 cases of low BA patients with spontaneous abortion and clinical observation indicated that good clinical effect was achieved after treatment, which was worthy of popularization and application. Chen Yun21used the Bazhen decotion in the treatment of RSA patients with low BA, the clinical observation of which proved that Bazhen Decoction was ef f ective. Zhou Ge22used Taishan Panshi Powder to improve the turning positive rate and pregnancy rate in treating kidney Yang def i ciency type RSA, which had the function of tonifying kidney and solidifying embryo. Li Zhang23used Buzhong Yiqi Dectotin in treating qi and xue def i ciency type BA negative patients, which increaseed BA efficiency.

WESTERN MEDICINE TREATMENT

Lymphocyte Immunotherapy, LIT

RSA patients spouses or unrelated individuals elbow venous blood was used for separation and purif i cation of lymphocytes, after being washed clean with physiological saline, it was diluted to living cells ＞ ＞ 3 xl07, then the patients received the forearm deltoid intradermal injection and subcutaneous injection every three weeks, four weeks formed a course of treatment. After two courses of treatment, then blocking antibody was detected, if the blocking antibody was positive, further sex life was guided, afterpregnancy, the treatment continued 3 to 6 courses. If the patients were still not pregnant after 3 months, repeated the treatment24,25. Spouse lymphocyte immune therapy was effective for mixed lymphocyte reaction in blocking antibody negative patients with unexplained recurrent miscarriage26. Numerous studies27suggested that LIT could raise the BA level of patients with recurrent abortion and increase the success rate of pregnancy. Wang Hekun28treated 120 BA lack of RSA patients, who were divided into 60 cases of the observation group and 60 cases of LIT group; LIT group increased pregnancy rate, improved the level of T lymphocyte. Gao weiwei29treated 149 cases of blocking antibody negative patients with recurrent abortion with active immunotherapy, after 4 months, the blocking antibody positive rate and pregnancy rate of patients improved, which lowered the risk of miscarriage. According to new fi nding30, LIT was more useful than that of the placebo, which meant using LIT before and during pregnancy was better than just before becoming pregnant, and treatment of low dose (less than 100 x 106 lymphocytes or 100 ml of peripheral blood) achieved good results.

Gama globulin (Intravenous Immunoglobulin, IVIG) passive immunotherapy

The presence of gamma globulin anti-trophoblast antigenspecific antibody was effective in treating RSA due to the lack of blocking antibody. Methods: Before pregnancy, the treatment was 0.5mg / kg, once every 2 weeks. Early pregnancy (pregnancy month was based on menstrual cycle, 8 to 10 days in any cycle or 5 weeks pregnancy had been reported), the treatment was at a dose 500-600mg/kg and once every 2 weeks, the dose was 300-400 mg/kg from 22 weeks to 24 weeks31. Most scholars believed that the immune globulin was beneficial to patients with recurrent abortion. Manfredi32pointed out that on 160 patients with recurrent miscarriage, immunoglobulin treatment increased the rate of pregnancy. Liu Juan33used small doses of immunoglobulin in treating 27 cases of BA negative recurrent miscarriage, after treatment, 21 cases turned positive, who had no obvious adverse reactions. However, some scholars put forward that the immune globulin treatment had no ef f ect in patients with recurrent miscarriage. Nazari34reported that heparin and aspirin combination and IVIG combined heparin and aspirin treatment of recurrent miscarriage scheme had no obvious difference, which proved that the application of heparin and aspirin was more suitable for the treatment of recurrent miscarriage compared to the use of IVIG, which avoided the usage of IVIG in complications and high costs. For immunoglobulin therapy had been controversial due to the side ef f ects of immunoglobulin therapy and being more expensive, which was rarely used in clinical practice.

INTEGRATION OF TRADITIONAL CHINESE AND WESTERN MEDICINE TREATMENT

Zhou Aixiang35confirmed the effect of the integration of traditional Chinese and western medicine treatment in treating 86 RSA patients with insufficient BA, who were randomly divided into pure LIT group and LIT combined with traditional Chinese medicine group. The results showed that BA turning positive time and the successful pregnancy rate of pure LIT group were lower than that of combination group, which proved that TCM with LIT treatment was more ef f ective in treating RSA patients with insufficient BA. Lai Youxing36treated 87 RSA patients with insufficient BA, who were divided into LIT group (41 cases) and combined treatment group (46 cases), after two course of treatment, the pregnancy rate of LIT group was 70.7%, and that of the combined treatment group was 89.1%. Zhou Xianwei37treated 40 low BA RSA patients with tonifying kidney and solidifying embryo granule joint LIT treatment, after treatment of 3 months, the BA positive rate was 95%, the pregnancy success rate was 94.74%. Lv Chunying38treated 48 cases by applying tonifying kidney and strengthening spleen principle combined LIT treatment, after a course of treatment BA positive rate was 83.3% while that of the western medicine group (24 cases) was 62.5%. Tian Dan39combined Modif i ed Buzhong Yiqi Decoction and LIT in treating spleen and kidney deficiency syndrome patients with insufficient BA, the therapy could promote the BA positive rate and improve the rate of pregnancy. Xu Xiaodong40treated 98 BA negative RSA patients, who were randomly divided into TCM and TCM combines LIT group, the results showed that the TCM group pregnancy rate was 48.98% and that of the joint group was 81.63%, which proved the significant effect of the combination, therefore, it was worthy of clinical popularization and application.

SUMMARY

The causes of RSA are complex, in the treatment of BA, LIT treatment can be applied in the treatment of patients with recurrent abortion, and however, there are still lots of disputes as for its application. Currently, the integration of traditional Chinese and western medicine treatment can improve BA positive rate and the pregnancy rate in treating RSA patients in the clinical practice; therefore, it is the trend of the future treatment of RSA.

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（Accepted: August 29, 2016）